Characterization the prognosis role and effects of snoRNAs in melanoma patients.

Melanoma is a melanocyte-derived malignant cancer and is known for its early metastasis and high mortality rates. It is a highly cutaneous tumour disease that could be related to the abnormal immune microenvironment, and the identification of reliable diagnostic and prognostic markers is crucial for improving patient outcomes. In the search for biomarkers, various types of RNAs have been discovered and recognized as reliable prognostic markers. Among these, small nucleolar RNAs (snoRNAs) have emerged as a promising avenue for studying early diagnosis and prognostic markers in tumours due to their widespread presence in tissues, tumour specificity and stability. In our study, we analysed snoRNAs data from melanoma samples in the TCGA-SKCM cohort and developed a prognostic model comprising 12 snoRNAs (SNORD9, SNORA31, SNORD14E, SNORA14A, SNORA5A, SNORD83A, SNORA75, AL096855, AC007684, SNORD14A, SNORA65 and AC004839). This model exhibited unique prognostic accuracy and demonstrated a significant correlation with the immune infiltration tumour microenvironment. Additionally, analysis of the GSE213145 dataset, which explored the sensitivity and resistance of immune checkpoint inhibitors, further supported the potential of snoRNAs as prognostic markers for immunotherapy. Overall, our study contributes reliable prognostic and immune-related biomarkers for melanoma patients. These findings can offer valuable insights for the future discovery of novel melanoma treatment strategies and hold promise for improving clinical outcomes in melanoma patients.

The romantic history of signaling pathway discovery in cell death: an updated review.

Cell death is a fundamental physiological process in all living organisms. Processes such as embryonic development, organ formation, tissue growth, organismal immunity, and drug response are accompanied by cell death. In recent years with the development of electron microscopy as well as biological techniques, especially the discovery of novel death modes such as ferroptosis, cuprotosis, alkaliptosis, oxeiptosis, and disulfidptosis, researchers have been promoted to have a deeper understanding of cell death modes. In this systematic review, we examined the current understanding of modes of cell death, including the recently discovered novel death modes. Our analysis highlights the common and unique pathways of these death modes, as well as their impact on surrounding cells and the organism as a whole. Our aim was to provide a comprehensive overview of the current state of research on cell death, with a focus on identifying gaps in our knowledge and opportunities for future investigation. We also presented a new insight for macroscopic intracellular survival patterns, namely that intracellular molecular homeostasis is central to the balance of different cell death modes, and this viewpoint can be well justified by the signaling crosstalk of different death modes. These concepts can facilitate the future research about cell death in clinical diagnosis, drug development, and therapeutic modalities.

Defined Surface Physicochemical Cues Inhibit M1 Polarization of Human Macrophages Using Colloidal Self-Assembled Patterns.

Biophysical and biochemical cues modulate mammalian cell behavior and phenotype simultaneously. Macrophages, indispensable cells in the innate immune system, respond to external threats such as bacterial infections and implanted devices, undergoing the classical M1 polarization to become a pro-inflammatory phenotype. In the study, lipopolysaccharide (LPS)-induced M1 polarization was examined using RAW264.7, THP-1, and primary human PBMCs on a family of artificial extracellular matrix (ECM), named colloidal self-assembled patterns (cSAPs). The results showed that cSAPs were biocompatible, which cannot induce M1 or M2 polarization. Interestingly, specific cSAPs (e.g., cSAP3) suppress the level of M1 polarization (i.e., reduced nitric oxide production, down-regulated gene expression of iNOS, IL-6, TNF-α, IL-1ß, and TLR4, and reduced proportion of CD11b+CD86+ cells). Transcriptome analysis showed that cell adhesion and cell-ECM interaction participated in the M1 polarization, and the mechano-sensitive genes such as PIEZO1 were down-regulated on the cSAP3. More interestingly, these genes were also down-regulated under LPS stimulation, indicating that cells became insensitive to the LPS. The abovementioned results indicate that the defined physicochemical cues can govern macrophage polarization. This study illustrates a potential surface design at biointerface, which is critical in tissue engineering and materiobiology. The outcome is also inspiring in ECM-mediated immune responses.